[Visual, hearing, and physical disability: prevalence and associated factors in a population-based study].
The aim of this study was to describe the prevalence of disabilities according to demographic and socioeconomic characteristics, as well as to determine the main causes. The research used data from two population-based health surveys in São Paulo State, Brazil, in 2002 and 2003, designed with complex sampling techniques. Interviewees that reported disabilities comprised the study sample, according to the database variables. Prevalence of any disability was 110.8; visual disability, 62; hearing disability, 44; and physical disability, 13.3. Prevalence rates for disabilities varied according to age, gender, and schooling. Prevalence of hearing and physical disability was higher among men. The principal cause of disabilities was the disease itself. External causes were also one of the causative factors in disabilities. Disabilities increased with age and were more prevalent among women and persons with less schooling, and the principal causes were diseases and injuries.


Vitamins D3 and K2 may partially counterbalance the detrimental effects of pentosidine in ex vivo human osteoblasts.
Osteoporosis is a metabolic multifaceted disorder, characterized by insufficient bone strength. It has been recently shown that advanced glycation end products (AGEs) play a role in senile osteoporosis, through bone cell impairment and altered biomechanical properties. Pentosidine (PENT), a wellcharacterized AGE, is also considered a biomarker of bone fracture. Adequate responses to various hormones, such as 1,25-dihydroxyvitamin D3, are prerequisites for optimal osteoblasts functioning. Vitamin K2 is known to enhance in vitro and in vitro vitamin D-induced bone formation. The aim of the study was to assess the effects of Vitamins D3 and K2 and PENT on in vitro osteoblast activity, to convey a possible translational clinical message. Ex vivo human osteoblasts cultured, for 3 weeks, with vitamin D3 and vitamin K2 were exposed to PENT, a well-known advanced glycoxidation end product for the last 72 hours. Experiments with PENT alone were also carried out. Gene expression of specific markers of bone osteoblast maturation [alkaline phosphatase, ALP; collagen I, COL Iα1; and osteocalcin (bone-Gla-protein) BGP] was measured, together with the receptor activator of nuclear factor kappa-B ligand/osteoproteregin (RANKL/OPG) ratio to assess bone remodeling. Expression of RAGE, a well-characterized receptor of AGEs, was also assessed. PENT+vitamins slightly inhibited ALP secretion while not affecting gene expression, indicating hampered osteoblast functional activity. PENT+vitamins up-regulated collagen gene expression, while protein secretion was unchanged. Intracellular collagen levels were partially decreased, and a significant reduction in BGP gene expression and intracellular protein concentration were both reported after PENT exposure. The RANKL/OPG ratio was increased, favouring bone reabsorption. RAGE gene expression significantly decreased. These results were confirmed by a lower mineralization rate. We provided in vitro evidence that glycoxidation might interfere with the maturation of osteoblasts, leading to morphological modifications, cellular malfunctioning, and inhibition of the calcification process. However, these processes may be all partially counterbalanced by vitamins D3 and K2. Therefore, detrimental AGE accumulation in bone might be attenuated and/or reversed by the presence or supplementation of vitamins D3 and K2.


Quality of parenting and vulnerability to depression: results from a family study.
We examined a group of subjects at familial risk of depression and explored the relationship between the perceptions of parents and a history of depression. We also investigated: (a) whether any difference in perceived parenting found between those with and without a past history of depression was an artefact of the depression; and (b) whether the relationship between parenting and depression was explained by neuroticism. We took a sample of first-degree relatives selected from a family study in depression and subdivided them by their history of mental illness on the SADS-L, into those: (a) without a history of mental illness (N = 43); and (b) those who had fully recovered from an episode of RDC major depression (N = 34). We compared the perceptions of parenting, as measured by the Parental Bonding Instrument (PBI), in these two groups having adjusted for the effect of neuroticism and subsyndromal depressive symptoms. We also had informants report on parenting of their siblings, the latter being subdivided into those with and without a past history of depression. Relatives with a past history of depression showed lower care scores for both mother and father combined compared with the never ill relatives. The presence of a history of depression was associated with a non-significant reduction in the self-report care scores compared to the siblings report. Vulnerable personality (as measured by high neuroticism) and low perceived care were both found to exert independent effects in discriminating between the scores of relatives with and without a history of depression and there was no interaction between them. This study confirmed that low perceived parental care was associated with a past history of depression, that it was not entirely an artefact of having been depressed, and suggested that this association was partially independent of neuroticism.


[Effect of electroacupuncture intervention on levels of SOD, GSH, GSH-Px, MDA, and apoptosis of dopaminergic neurons in substantia Nigra in rats with Parkinson's disease].
To observe the effect of electroacupuncture (EA) on superoxide (SOD), glutathione peroxidase (GSH-Px) activity, contents of glutathione (GSH) and malondiadehyde (MDA), and expression of tyrosine hydroxylase (TH) and apoptosis of Dopaminergic (DA) neurons in Substantia Nigra of rats with Parkinson's disease (PD). Adult male Wistar rats were randomly divided into normal (10 rats), model (11 rats), EA (11 rats) and medication (11 rats) groups. The PD model was established by i.h. of Rotenone (0.8 mg/kg) for 28 days. EA stimulation (2 Hz/80 Hz, 2 mA) was applied at "Baihui" (GV 20), "Sanyinjiao" (SP 6) and "Taichong" (LR 3) acupoints for 10 min, once per day for 14 times. For rats in the medication group, Madopar suspension fluid (1.67 mg/kg) was given by gavage for 14 days. Xanthine oxidase method and colorimetric ana- lysis method were used to examine the SOD, GSH-Px activity and contents of GSH and MDA in the Substantia Nigra tissue of the right brain, respectively. Immunohistochemical technique was used to detect the TH positive neurons and TUNEL method was used to examine the apoptosis of DA neurons of the Substantia Nigra in the left brain. Following the intervention, the decreased SOD and GSH-Px activity, GSH contents, and the increased MDA content of the Substantia Nigra in PD rats were obviously reversed by EA intervention (P < 0.05) but not by medication except MDA content (P > 0.05). In comparison with the model group, the decreased TH immunoactivity, and the increased numbers of apoptotic cells of DA neurons were apparently suppressed in both EA and medication groups (P < 0.05), but without significant differences between the EA and the medication groups (P > 0.05). In addition, HE stain showed that EA intervention could improve PD-induced impairment of Substantia Nigra neurons (mild swelling of neurons with large nucleus and deranged fibers). EA intervention can reduce pathological changes of Substantial Nigra in PD rats, which is probably associated with its effects in up-regulating the SOD and GSH-Px activity, GSH contents, and down-regulating MDA level, and reducing the apoptosis of DA neurons of the Substantia Nigra, suggesting an anti-oxidative stress effect of EA therapy.


Awareness promotion about excessive gambling among video lottery retailers.
This paper describes and evaluates "As luck would have it," an awareness program completed by retailers in Quebec Province. This program, which is presented as a two-hour awareness promotion workshop, aimed to inform retailers about excessive gambling. More specifically, it provided answers to the following questions: (1) What is chance and randomness? (2) Is there a link between misunderstanding the concept of chance and excessive gambling? (3) How does one recognise the symptoms of this disorder? (4) How should retailers intervene if they decide to do so? Results showed that retailers developed a better understanding of problem gambling, could recognise its main symptoms, felt more capable of coping with excessive gamblers, and of choosing the most appropriate moment to do so. In the follow-up phase, retailers who had attended the workshop reported that they approached a problem gambler significantly more often than the retailers who had not attended the workshop, and had discussed how to help problem gamblers significantly more often. The practical implications of these results are briefly discussed.


Tax havens and global environmental degradation.
The release of classified documents in the past years have offered a rare glimpse into the opaque world of tax havens and their role in the global economy. Although the political, economic and social implications related to these financial secrecy jurisdictions are known, their role in supporting economic activities with potentially detrimental environmental consequences have until now been largely ignored. Here, we combine quantitative analysis with case descriptions to elaborate and quantify the connections between tax havens and the environment, both in global fisheries and the Brazilian Amazon. We show that while only 4% of all registered fishing vessels are currently flagged in a tax haven, 70% of the known vessels implicated in illegal, unreported and unregulated fishing are, or have been, flagged under a tax haven jurisdiction. We also find that between October 2000 and August 2011, 68% of all investigated foreign capital to nine focal companies in the soy and beef sectors in the Brazilian Amazon was transferred through one, or several, known tax havens. This represents as much as 90-100% of foreign capital for some companies investigated. We highlight key research challenges for the academic community that emerge from our findings and present a set of proposed actions for policy that would put tax havens on the global sustainability agenda.


Multiple founder events explain the genetic diversity and structure of the model allopolyploid grass Brachypodium hybridum in the Iberian Peninsula hotspot.
It is accepted that contemporary allopolyploid species have originated recurrently, but very few cases have been documented using multiple natural formations of the same species. To extend our knowledge, we have investigated the multiple origins, genetic variation and structure of the allotetraploid grass Brachypodium hybridum with respect to its progenitor diploid species B. distachyon (D genome) and B. stacei (S genome). For this, our primary focus is the Iberian Peninsula, an evolutionary hotspot for the genus Brachypodium. We analysed 342 B. hybridum individuals from 36 populations using ten nuclear SSR loci and two plastid loci. The B. hybridum genetic profiles were compared with those previously reported for B. stacei and B. distachyon. In addition, phylogenetic analysis of the plastid data was performed for a reduced subset of individuals. The nuclear simple sequence repeat (SSR) genetic analysis detected medium to high genetic diversity, with a strong south-to-north genetic structure cline, and a high selfing rate in B. hybridum. Comparative genetic analysis showed a close relatedness of current B. hybridum D allelic profiles with those of B. distachyon, but a lack of similarity with those of B. stacei, suggesting another B. stacei source for the B. hybridum S alleles. Plastid analysis detected three different bidirectional allopolyploidization events: two involved distinct B. distachyon-like ancestors and one involved a B. stacei-like ancestor. The south-eastern Iberian Peninsula B. hybridum populations were more genetically diverse and could have originated from at least two hybridization events whereas north-eastern/north-western Iberian Peninsula B. hybridum populations were less diverse and may have derived from at least one hybridization event. The genetic and evolutionary evidence supports the plausible in situ origin of the south-eastern and northern Iberian Peninsula B. hybridum allopolyploids from their respective local B. distachyon and unknown B. stacei ancestors. The untapped multiple origins and genetic variation detected in these B. hybridum populations opens the way to future evolutionary analysis of allopolyploid formation and genomic dominance and expression in the B. hybridum-B. distachyon-B. stacei grass model complex.


Diflunisal in the Treatment of the Pain of Osteoarthritis Summary of Clinical Studies.
In comprehensive clinical studies, diflunisal - a new nonsteroidal antiinflammatory drug with a long duration of action - was shown to be highly effective and generally well tolerated in the short- and long-term treatment of the pain of osteoarthritis. In double-blind comparison studies, diflunisal was comparable in efficacy to aspirin and better tolerated. In a separate study with ibuprofen, 800 to 1,200 mg daily (manufacturer's present recommended dose, 900 to 2,400 mg daily), diflunisal, 500 to 750 mg daily, was more effective and comparable in tolerability. Diflunisal had a longer duration of action, requiring only twice-a-day dosage.


Inducible L-alanine exporter encoded by the novel gene ygaW (alaE) in Escherichia coli.
We previously isolated a mutant hypersensitive to L-alanyl-L-alanine from a non-L-alanine-metabolizing Escherichia coli strain and found that it lacked an inducible l-alanine export system. Consequently, this mutant showed a significant accumulation of intracellular L-alanine and a reduction in the L-alanine export rate compared to the parent strain. When the mutant was used as a host to clone a gene(s) that complements the dipeptide-hypersensitive phenotype, two uncharacterized genes, ygaW and ytfF, and two characterized genes, yddG and yeaS, were identified. Overexpression of each gene in the mutant resulted in a decrease in the intracellular l-alanine level and enhancement of the L-alanine export rate in the presence of the dipeptide, suggesting that their products function as exporters of L-alanine. Since ygaW exhibited the most striking impact on both the intra- and the extracellular L-alanine levels among the four genes identified, we disrupted the ygaW gene in the non-L-alanine-metabolizing strain. The resulting isogenic mutant showed the same intra- and extracellular L-alanine levels as observed in the dipeptide-hypersensitive mutant obtained by chemical mutagenesis. When each gene was overexpressed in the wild-type strain, which does not intrinsically excrete alanine, only the ygaW gene conferred on the cells the ability to excrete alanine. In addition, expression of the ygaW gene was induced in the presence of the dipeptide. On the basis of these results, we concluded that YgaW is likely to be the physiologically most relevant exporter for L-alanine in E. coli and proposed that the gene be redesignated alaE for alanine export.


Ascorbic acid degradation in a model apple juice system and in apple juice during ultraviolet processing and storage.
Ultraviolet radiation induced degradation of ascorbic acid in a model apple juice system and in apple juice was studied using a collimated beam batch UV reactor. In the model system, ascorbic acid degradation was more rapid at higher dose levels and the reaction accelerated with increasing exposure time. Ascorbic acid degradation significantly (P < 0.05) increased as the pH was raised from 2.4 to 5.5, although no difference was observed between 2.4 and 3.3. Increasing malic acid concentration between 0.1 and 1%, increased ascorbic acid degradation (P < 0.05) although there was no difference between 0.5 and 1.0%. Solution absorbance, varied by addition of tannic acid, decreased ascorbic acid degradation with increasing concentration due to absorption of UV radiation. Fructose at levels found in apple juice significantly increased ascorbic acid degradation while glucose and sucrose did not. Factors identified that accelerate ascorbic acid degradation may at least partially explain why ascorbic acid degradation occurred more rapidly in UV-treated apple juice than in the 0.5% malic acid model system. Ascorbic acid degradation continued after UV treatments during dark storage. Storage decreases were faster at higher initial UV dose levels and higher storage temperature. The present study shows the effect of UV processing on ascorbic acid, a key vitamin found in many fruit juices. Process developers and researchers can use this study as a model for designing experiments to identify factors that influence the stability of vitamin C and other bioactive compounds during UV processing.


Neonatal respiratory distress in a reference neonatal unit in Cameroon: an analysis of prevalence, predictors, etiologies and outcomes.
Neonatal respiratory distress (NRD) is a main cause of neonatal morbidity and mortality in developing countries. Early detection of its risk factors and early treatment of its etiologies are major challenges. However, few studies in developing countries have provided data needed to tackle it. We aimed to determine the prevalence, predictors, etiologies and outcome of NRD in a tertiary health care centre of Cameroon. We analyzed the hospital files of all newborns admitted to the Neonatal unit of Douala General Hospital from 1(st) January 2011 to 28(th) February 2013. NRD was diagnosed based on the presence of one or more of the following signs: an abnormal respiratory rate, expiratory grunting, nasal flaring, chest wall recessions and thoraco-abdominal asynchrony with or without cyanosis, in their files. Socio-demographic and clinical variables of newborns and their mothers were analyzed using logistic regression analysis. The prevalence of NRD was 47.5% out of the 703 newborns studied. Acute fetal distress, elective caesarean delivery, APGAR score < 7 at the 1(st) minute, prematurity, male gender and macrosomia were independent predictors of NRD. The main etiologies were neonatal infections (31%) and transient tachypnea of the newborn (25%). Its neonatal mortality rate was 24.5%, mainly associated with neonatal sepsis and hyaline membrane disease. NRD is a frequent emergency and causes high morbidity and mortality. Most of its risk factors and etiologies are preventable. Adequate follow-up of pregnancy and labor for timely intervention may improve the neonatal outcomes.


Trajectories in quality of life of patients with a fracture of the distal radius or ankle using latent class analysis.
This prospective study aimed to identify the different trajectories of quality of life (QOL) in patients with distal radius fractures (DRF) and ankle fractures (AF). Secondly, it was examined if subgroups could be characterized by sociodemographic, clinical, and psychological variables. Patients (n = 543) completed the World Health Organization Quality of Life assessment instrument-Bref (WHOQOL-Bref), the pain, coping, and cognitions questionnaire, NEO-five factor inventory (neuroticism and extraversion), and the state-trait anxiety inventory (short version) a few days after fracture (i.e., pre-injury QOL reported). The WHOQOL-Bref was also completed at three, six, and 12 months post-fracture. Latent class trajectory analysis (i.e., regression model) including the Step 3 method was performed in Latent Gold 5.0. The number of classes ranged from three to five for the WHOQOL-Bref facet and the four domains with a total variance explained ranging from 71.6 to 79.4%. Sex was only significant for physical and psychological QOL (p < 0.05), whereas age showed significance for overall, physical, psychological, and environmental QOL (p < 0.05). Type of treatment or fracture type was not significant (p > 0.05). Percentages of chronic comorbidities were 1.8 (i.e., social QOL) to 4.5 (i.e., physical QOL) higher in the lowest compared to the highest QOL classes. Trait anxiety, neuroticism, extraversion, pain catastrophizing, and internal pain locus of control were significantly different between QOL trajectories (p < 0.05). The importance of a biopsychosocial model in trauma care was confirmed. The different courses of QOL after fracture were defined by several sociodemographic and clinical variables as well as psychological characteristics. Based on the identified characteristics, patients at risk for lower QOL may be recognized earlier by health care providers offering opportunities for monitoring and intervention.


Healthcare infrastructure and emotional support are predictors of CD4 cell counts and quality of life indices of patients on antiretroviral treatment in Free State Province, South Africa.
While many AIDS patients in sub-Saharan Africa are receiving antiretroviral treatment (ART) via public clinics, improvements in health status also depend on socioeconomic and psychological factors and quality of healthcare services. Inter-dependence between patients' clinical markers and quality of life indicators should be analyzed using comprehensive models. This longitudinal study compiled socioeconomic and clinical variables at six monthly intervals on patients receiving ART in South Africa; patients' ratings of quality of services and staff in "Assessment" and "Treatment" sites were assessed. Dynamic random effects models were estimated by maximum likelihood for CD4 cell counts and for quality of life indices (EQ-5D and Visual Analogue Scale), incorporating the inter-dependence between plasma HIV RNA levels and CD4 cell counts. The results showed that emotional support received by patients was a significant predictor (P<0.05) of CD4 cell counts and quality of life indices. Ratings of services and staff in Assessment and Treatment sites were significantly associated with CD4 cell counts and quality of life indices; CD4 cell count was a significant predictor of quality of life indices. The results indicated that it is important to compile socioeconomic and psychological variables for AIDS patients and monitor healthcare services for improving their health status and quality of life.


Interparental Conflict and Early Adolescent Depressive Symptoms: Parent-Child Triangulation as the Mediator and Grandparent Support as the Moderator.
A notable ambiguity persists concerning whether distinct forms of parent-child triangulation (unstable coercive coalition, stable coalition, detouring-attacking, detouring supportive, parentification) might mediate the association between interparental conflict and early adolescent depressive symptoms similarly within the context of Chinese Confucianism. Filling this research gap, this study aimed to examine the mediating role of the five dimensions of parent-child triangulation in the association between interparental conflict and early adolescent depressive symptoms, as well as the moderating effect of grandparent support on this mediating pathway. Data were drawn from a sample of 761 Chinese adolescents (M age = 12.82 ± 0.47, 49.1% girls). Structural equation model analyses indicated that unstable coercive coalition, stable coalition, and detouring-attacking behaviors partially mediated the association between interparental conflict and adolescent depressive symptoms, while detouring-supportive behaviors and parentification did not demonstrate such mediating effects. Unlike Western societies, a negative correlation was observed between interparental conflict and parentification in the context of China. Grandparent support mitigated the adverse effects of both interparental conflict and the unstable coercive coalition on early adolescent depressive symptoms.


A pilot study on the prevalence of DNA palindromes in breast cancer genomes.
DNA palindromes are a unique pattern of repeat sequences that are present in the human genome. It consists of a sequence of nucleotides in which the second half is the complement of the first half but appearing in reverse order. These palindromic sequences may have a significant role in DNA replication, transcription and gene regulation processes. They occur frequently in human cancers by clustering at specific locations of the genome that undergo gene amplification and tumorigenesis. Moreover, some studies showed that palindromes are clustered in amplified regions of breast cancer genomes especially in chromosomes (chr) 8 and 11. With the large number of personal genomes and cancer genomes becoming available, it is now possible to study their association to diseases using computational methods. Here, we conducted a pilot study on chromosomes 8 and 11 of cancer genomes to identify computationally the differentially occurring palindromes. We processed 69 breast cancer genomes from The Cancer Genome Atlas including serum-normal and tumor genomes, and 1000 Genomes to serve as control group. The Biological Language Modelling Toolkit (BLMT) computes palindromes in whole genomes. We developed a computational pipeline integrating BLMT to compute and compare prevalence of palindromes in personal genomes. We carried out a pilot study on chr 8 and chr 11 taking into account single nucleotide polymorphisms, insertions and deletions. Of all the palindromes that showed any variation in cancer genomes, 38% of what were near breast cancer genes happened to be the most differentiated palindromes in tumor (i.e. they ranked among the top 25% by our heuristic measure). These results will shed light on the prevalence of palindromes in oncogenes and the mutations that are present in the palindromic regions that could contribute to genomic rearrangements, and breast cancer progression.


[Features of the formation and reproduction of various conditioned responses during rat ontogeny].
Developmental characteristics are described of some conditioned excitatory and inhibitory defense reactions. Typical periods of learning speed and efficacy culmination are shown and compared with the periods of memory culmination. The learning and memory culmination period however do not coincide, they depend on the type of reaction, on the actual experimental conditions and on gender of the animals. The process of memory retrieval has also its typical developmental characteristics, and especially the time course of memory retrieval of partly learned active avoidance is of interest in rats of 4 - 6 weeks of age. Here the retrieval curve within 1 hour after learning has a "W" shape with two minima in the 10th and 40th minute which can be altered by some experimental procedures, such as REM-sleep deprivation, environmental stimulation, or pharmacologically. An inhibitory conditioned reaction was established in the newborn rat by means of a special method of passive avoidance which represents the earliest evidence of inhibitory conditioning in the ontogeny of mammals.


A revised excitotoxic hypothesis of schizophrenia: therapeutic implications.
A revision of an "excitotoxic hypothesis" of schizophrenia is summarized. The hypothesis suggests that in, at least, a subtype of patients with schizophrenia, progressive excitotoxic neuronal cell death in hippocampal and cortical areas occurs via "disinhibition" of glutamatergic projections to these areas. Patients who have excitotoxic damage would be expected to have poor outcomes characterized, perhaps, by anatomic evidence of progressive neurodegeneration, pronounced negative symptoms and cognitive deficits, and profound psychosocial deterioration. Disinhibited glutamatergic activity could result from inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission and a consequent failure to stimulate inhibitory gamma-aminobutyric acid (GABA)-ergic interneurons, and/or anatomic degeneration of inhibitory GABAergic interneurons. The result of these hypothesized mechanisms is excessive stimulation of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate class of glutamate receptor complexes. In turn, this excessive stimulation of AMPA/kainate receptors could lead to disruption of ionic gradients, depletion of energy reserves expended in an attempt to restore and maintain the ionic disequilibrium across neuronal membranes, generation of reactive oxygen species, and cell death from apoptotic and other mechanisms. The postulated existence of disinhibited glutamatergic neurotransmission and the subsequent cascade of excitotoxic events resulting from NMDA receptor hypofunction (NRH), anatomic degeneration of inhibitory GABAergic interneurons, or a combination of the two has suggested a diverse variety of experimental therapeutic interventions for schizophrenia. These interventions include facilitation of NMDA receptor-mediated neurotransmission, potentiation of GABAergic neurotransmission, antagonism of AMPA/kainate receptors, and "quenching" of locally generated reactive oxygen species. In fact, several of these approaches have already been pursued or are proposed as part of a systematic clinical investigation of the revised excitotoxic hypothesis of schizophrenia.


Neuroendocrine control of follicle-stimulating hormone (FSH) secretion. I. Direct evidence for separate episodic and basal components of FSH secretion.
Continuous sampling of hypophyseal portal blood from unrestrained sheep is providing an unprecedented means for measuring and defining the characteristics of the secretory profile of GnRH. With this method, GnRH has been shown to be released in discrete pulses lasting 5-8 min, with the amplitude of some pulses exceeding 50-fold. Although the relationship between these pulses and the accompanying pulses of LH measured in the jugular vein are unambiguous, the relationship of GnRH pulses to the release of FSH has not been well defined due to the longer clearance of FSH. In previous studies we have shown that hypophyseal portal blood, in addition to serving as a source material for hypothalamic secretions, provides a means to define secretory patterns of pituitary hormones. Because of this we hypothesized that the GnRH-FSH secretory relationship would be easier to define in hypophyseal portal than in jugular vein blood before the secretory products are subjected to dispersion and clearance in circulation. To test this possibility, we monitored hormonal patterns in blood collected at 5-min intervals for 6-12 h from the peripheral and hypophyseal portal circulation of six ovariectomized ewes from a previous study. In contrast to the nonpulsatile pattern of FSH in the peripheral blood, 93% of the GnRH pulses were associated with essentially coincident, discrete pulses of FSH in the portal plasma. Of potentially even greater interest, additional episodes of FSH release were clearly discernible between the GnRH-associated pulses of FSH. As concentrations of peripheral plasma FSH did not reach those in hypophyseal portal plasma, the inter-GnRH episodes of FSH secretion could not result from contaminating peripheral blood. In addition to the episodic mode of secretion, substantial amounts of FSH were found between FSH pulses. This basal component of FSH appeared to be the dominant mode of secretion rather than pulses. The results of this study not only confirm that GnRH pulses lead to pulsatile release of FSH, they also suggest that some other mechanism or factor may be controlling the non-GnRH-associated episodes as well as the basal components of FSH secretion.


In vitro characterization of cardiac radiofrequency ablation lesions using optical coherence tomography.
Currently, cardiac radiofrequency ablation (RFA) is guided by indirect signals. We demonstrate optical coherence tomography (OCT) characterization of RFA lesions within swine ventricular wedges. Untreated tissue exhibited a consistent birefringence artifact within OCT images due to the organized myocardium, which was not present in treated tissue. Birefringence artifacts were detected by filtering with a Laplacian of Gaussian (LoG) to quantify gradient strength. The gradient strength distinguished RFA lesions from untreated sites (p=5.93 x 10(-15)) with a sensitivity and specificity of 94.5% and 86.7% respectively. This study demonstrates the potential of OCT for monitoring cardiac RFA, confirming lesion formation and providing feedback to avoid complications.


Chronic Wounds in Burn Injury: A Case Report on Importance of Biofilms.
According to the National Institutes of Health and the Center for Disease and Prevention, it is estimated that 65 to 80 percent of the human infectious are caused by biofilms. Antibiotics and drainage of purulent discharge are the main treatment measures. But in chronic infections sometimes these findings are not easy to recognize. Biofilm is an extracellular polymeric conglomeration generally composed of extracellular DNA, proteins, and polysaccharides, which help bacteria to survive into the host. The following case is the example of chronic wound in burn patient, where biofilm gets involved and special attention is given to the relationship biofilm-chronic wound injury in a burn patient.


Infections in hematogical cancer patients: the contribution of systematic reviews and meta-analyses.
Systematic reviews and meta-analyses have made a major contribution to the evidence-based management of infections in cancer patients. We review the contribution of systematic reviews with regard to antibiotic, antifungal, antiviral and Pneumocystis pneumonia prophylaxis; antibiotic and antifungal treatment of febrile neutropenia; use of intravenous immunoglobulins, and infection control strategies during neutropenia. We focus on limitations of randomized controlled trials and the way systematic reviews have addressed and resolved some of these limitations. Systematic reviews allow us to ask the right clinical question; consider the most relevant clinical outcome; address the problem of small trials and rare outcomes; address external validity and bias in randomized controlled trials, and point at gaps in evidence.


Increased prevalence of metabolic syndrome in uncontrolled hypertension across Europe: the Global Cardiometabolic Risk Profile in Patients with hypertension disease survey.
The Global Cardiometabolic Risk Profile in Patients with hypertension disease survey investigated the cardiometabolic risk profile in adult outpatients with hypertension in Europe according to the control of blood pressure (BP) as defined in the European Society of Hypertension and of the European Society of Cardiology (ESH/ESC) guidelines. Data on BP control and cardiometabolic risk factors were collected for 3370 patients with hypertension in 12 European countries. Prevalence was analyzed according to BP status and ATP III criteria for metabolic syndrome. BP was controlled (BP < 140/90 mmHg for nondiabetic patients; BP < 130/80 mmHg for diabetic patients) in 28.1% of patients. Patients with uncontrolled BP had significantly higher mean weight, BMI, waist circumference, fasting blood glucose, total cholesterol and triglycerides and high-density lipoprotein cholesterol levels were significantly lower (women only) compared with patients with controlled BP (P < 0.05). The prevalence of metabolic syndrome and type 2 diabetes was also significantly higher in patients with uncontrolled BP compared with controlled BP (P < 0.001) (metabolic syndrome: 66.5 versus 35.5%; diabetes 41.1 versus 9.8%, respectively). 95.3% of patients with both metabolic syndrome and type 2 diabetes had uncontrolled BP. In a multivariate analysis, diabetes and metabolic syndrome were found to be associated with a high risk of poor BP control: odds ratio, 2.56 (metabolic syndrome); 5.16 (diabetes). In this European study, fewer than one third of treated hypertensive patients had controlled BP. Metabolic syndrome and diabetes were important characteristics associated with poor BP control. Thus, more focus is needed on controlling hypertension in people with high cardiometabolic risk and diabetes.


Regulation of the hypophysiotropic secretions of the brain.
Two elements govern the secretion of the anterior pituitary. One influence, from the hypothalamus is mediated by the hypothalamic hypophysiotrophic hormones, which are elaborated in specialized neurones and reach the pituitary by way of the hypophysial-portal vessels. The other influence is the feedback control exerted by target gland hormones directly on the pituitary, and possibly on the hypothalamus as well. In the case of the pituitary-thyroid axis, thyroid hormone exerts a direct inhibitory effect on TSH secretion, interacting with the stimulatory effects of thryotrophin releasing hormone (TRH). In the rat, TRH excretion in the urine is reduced by thyroid deficiency, suggesting that the thyroid hormones may also be involved in regulating TRH secretion, but we cannot be certain that the effect is on hypothalamic TRH secretion, since TRH also is found in other parts of the brain. In the case of pituitary-goned control, estrogens inhibit pituitary responsiveness to luteinizing hormone releasing hormone (LRH) in men, but sensitize the pituitary in women. In men, estrogens stimulate LRH release as inferred from changes in plasma bioassayable luteinizing hormone-releasing factor (LRF) activity, thus suggesting a positive feedback effect of estrogens on the hypothalamus. In women, LRF activity appears in the blood during midcycle, suggesting that mid-cycle LRH secretion, together with estrogen sensitization of the pituitary, are components of the mechanism underlying the midcycle ovulatory surge.


Understanding the complexity of ambivalence toward pregnancy: does it predict inconsistent use of contraception?
Ambivalence towards future pregnancy is common and may increase the risk of unprotected sex and unintended pregnancy. We propose that ambivalent attitudes toward pregnancy consist of subtypes that are differentially associated with contraceptive use. Using data from a nationally representative survey of unmarried young adults (N = 1,147), we constructed four categories of ambivalence based on attitudes toward a hypothetical pregnancy. Multivariate analyses examined characteristics of ambivalence and the association between ambivalence and contraceptive use. Approximately one third of sexually active unmarried young adults are ambivalent about pregnancy. Having positive ambivalence (important to avoid a pregnancy but would be happy if it occurred) is associated with age, gender, education, and Hispanic origin. Although ambivalence toward pregnancy is associated with lower contraceptive use, this is true only among women with negative ambivalence (not important to avoid a pregnancy but would be unhappy if a pregnancy occurred). Attitudes toward pregnancy are multifaceted, and a more nuanced understanding of women's attitudes toward pregnancy can help target prevention programs and related policies for women at risk of unintended pregnancy.


Electrophysiological correlates of semantic processing in Williams syndrome.
Williams syndrome (WS), a genetic neurodevelopmental disorder due to microdeletion in chromosome 7, has been described as a syndrome with an intriguing socio-cognitive phenotype. Cognitively, the relative preservation of language and face processing abilities coexists with severe deficits in visual-spatial tasks, as well as in tasks involving abstract reasoning. However, in spite of early claims of the independence of language from general cognition in WS, a detailed investigation of language subcomponents has demonstrated several abnormalities in lexical-semantic processing. Nonetheless, the neurobiological processes underlying language processing in Williams syndrome remain to be clarified. The aim of this study was to examine the electrophysiological correlates of semantic processing in WS, taking typical development as a reference. A group of 12 individuals diagnosed with Williams syndrome, with age range between 9 and 31 years, was compared with a group of typically developing participants, individually matched in chronological age, gender and handedness. Participants were presented with sentences that ended with words incongruent (50%) with the previous sentence context or with words judged to be its best completion (50%), and they were asked to decide if the sentence made sense or not. Results in WS suggest atypical sensory ERP components (N100 and P200), preserved N400 amplitude, and abnormal P600 in WS, with the latter being related to late integration and re-analysis processes. These results may represent a physiological signature of underlying impaired on-line language processing in this disorder.


Why do patients with faecal impaction have faecal incontinence.
To elucidate the phenomenon of faecal incontinence in impacted patients, manometric, radiological and other investigations were carried out in 55 elderly patients, who had impacted masses of faeces in the rectum and were incontinent of faeces and 36 elderly control subjects with no anorectal problems. Maximum basal pressure and the maximum squeeze pressure in impacted patients were not significantly different from elderly controls. Sphincter pressures were no different after disimpaction than they were with faecal masses in situ, suggesting that leakage and soiling were not caused by stretching of the anal ring or prolonged reflex inhibition of anal tone by the faecal mass. The anorectal angle was more obtuse in impacted patients than in elderly controls though there was no greater degree of perineal descent. Anal and perianal sensation was impaired in impacted patients compared with controls. Rectal sensation was also impaired in the impacted patients in that the volume in a rectal balloon that could be perceived by the subject and the volume that gave rise to a desire to defecate were much higher in impacted patients than in controls. The rectal volume required to cause anal relaxation was lower in impacted patients compared with controls though there was no reduction in the volume at which anal relaxation failed to recover its resting tone. Rectal distension elicited external sphincter contractions in 53% impacted patients compared with 80% of controls. In conclusion, faecal soiling in patients with faecal impaction is probably related to the combination of an obtuse anorectal angle and the low anal pressures, normally found in the elderly and to impaired anorectal sensation which prevents conscious contraction of the external sphincter when the internal sphincter is relaxed.


Neurosteroid inhibition of cell death.
Diverse gamma-aminobutyric acid (GABAA) receptor modulators exhibited novel cytoprotective effects and mechanisms of action in rabbit renal proximal tubules subjected to mitochondrial inhibition (antimycin A) or hypoxia. Cytoprotective potencies (50% effective concentration, EC50) were 0.3 nM allopregnanolone (AP) > 0.4 nM 17 alpha-OH-allopregnanolone (17 alpha-OH-AP) > 30 nM dehydroepiandrosterone sulfate (DHEAS) = 30 nM pregnenolone sulfate (PS) > 500 nM pregnenolone (PREG) > 30 microM muscimol > 10 mM GABA following antimycin A exposure. Maximal protection with AP and 17 alpha-OH-AP was 70%, whereas DHEAS, PS, PREG, and muscimol produced 100% cytoprotection. Experiments with AP, PS, and muscimol revealed the return of mitochondrial function and active Na+ transport following hypoxia/reoxygenation. Muscimol inhibited the antimycin A-induced influx of both extracellular Ca2+ and Cl- that occurs during the late phase of cell injury, whereas the neurosteroids only inhibited influx of Cl-. Radioligand binding studies with AP and PS did not reveal a specific binding site; however, structural requirements were observed for cytoprotective potency and efficacy. In conclusion, we suggest that the GABAA receptor modulators muscimol and neurosteroids are cytoprotective at different cellular sites in the late phase of cell injury; muscimol inhibits Ca2+ and subsequent Cl- influx, whereas the neurosteroids inhibit Cl- influx.


The tnpA and tnpD gene products of the Spm element are required for transposition in tobacco.
The maize Suppressor-mutator (Spm) element encodes four alternatively spliced transcripts designated tnpA, tnpB, tnpC, and tnpD. tnpA and tnpB are monocistronic, whereas tnpC and tnpD are dicistronic, and the protein-coding sequences of each transcript overlap extensively with those of one or more of the other transcripts. We have analyzed the role of the Spm-encoded gene products in element transposition by using cDNAs with a single open reading frame to (1) complement Spm elements with frameshift mutations and (2) complement each other in a tobacco transposition assay. We report that whereas the tnpA and tnpD gene products are essential for transposition, the tnpB and tnpC gene products are not. We have analyzed the structure of empty donor sites, new insertion sites, and potential transposition intermediates. We discuss the implications of our findings for the mechanism of Spm transposition.


[Basocellular carcinoma in a smallpox vaccination scar].
A 52 year old housewife was vaccinated against smallpox at the age of 18, on her right deltoid area. At the age of 50 she noticed erythema and scaling on the vaccination scar and 2 years later a nodule appear that enlarged during the following 3 months. There was no history nor skin changes suggestive of significant sun exposure. The histological examination of an initial biopsy and of the subsequently excised lesion revealed a basal cell carcinoma of the solid type. The relevant literature was reviewed and discussed with emphasis on sex and age incidence, age and site of vaccination, free interval between inoculation and tumor appearance, coexistence or not of other sun induced neoplasias and precancerous lesions and other possibly relevant clinical and etiopathogenetic aspects.


Rapid and sensitive PCR detection of Vibrio penaeicida, the putative etiological agent of syndrome 93 in New Caledonia.
Experimental infections of Penaeus (Litopenaeus) stylirostris were performed with a Vibrio penaeicida strain (AM101) isolated in New Caledonia from Syndrome 93 diseased shrimp. Cumulative mortalities resulting from intramuscular injection or immersion of shrimp in bacterial suspensions demonstrated high virulence for this bacterial strain and suggested that V. penaeicida could be the etiological agent of Syndrome 93. The median lethal dose (LD50) for AM101 was 1.3 x 10(4) CFU (colony forming units) ml-1 by immersion and less than 5 CFU shrimp-1 by intramuscular challenge, with mortality outbreaks at 48 and 22 h after challenge, respectively. A polymerase chain reaction (PCR) detection assay using a primer set designed from the 16S ribosomal RNA gene of V. penaeicida was developed. It gave an expected amplicon of approximately 310 bp in ethidium bromide-stained agarose gels. The specificity of these primers was assessed with different Vibrio species. Furthermore, DNA extracted by the Chelex method could be used to detect fewer than 20 cultured Vibrio cells in sea-water or shrimp hemolymph by this assay. It appears to be a reliable screening method for detecting V. penaeicida in shrimp and from the aquatic environment.


Protocol for systematic review of school-based interventions to prevent and control obesity in African learners.
The increasing prevalence of obesity and overweight in childhood in developing countries is a public health concern to many governments. Schools play a significant role in the obesity epidemic as well as provide favourable environments for change in behaviours in childhood which can be carried on into adulthood. There is dearth of information on intervention studies in poor-resource settings. This review will summarise the available evidence on school-based interventions that focused on promoting healthy eating and physical activity among learners aged 6-15 years in Africa and to identify factors that lead to successful interventions or potential barriers to success of these programmes within the African context. This protocol is developed following the guidelines of PRIMSA-P 2015. Relevant search terms and keywords generated from the subject headings and the African search filter will be used to conduct a comprehensive search of MEDLINE (PubMed), MEDLINE (EbscoHost), CINAHL (EbscoHost), Register Academic Search Complete (EbscoHost) and ISI Web of Science (Science Citation Index) for published literature on school-based interventions to prevent and control obesity in learners in Africa. Grey literature will be also be obtained. The searches will cover 1 January 2000 to 30 June 2016. No language limitations will be applied. Full-text articles of eligible studies will be screened. Risk of bias and quality of reporting will be assessed. Data will be extracted, synthesised and presented by country and major regional groupings. Meta-analysis will be conducted for identical variables across studies, where data allow. This protocol is developed following the guidelines of PRISMA-P 2015. No primary data will be collected hence ethics is not a requirement. The findings will be submitted for publication in peer-reviewed journals, in conferences and in policy documents for decision-making, where needed.


The lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in epithelial ovarian carcinoma.
Highly upregulated in liver cancer (HULC) is a long noncoding RNA (lncRNA), which has recently been identified as a key regulator in the progression of hepatocellular carcinoma, gliomas and gastric cancer. However, its role in epithelial ovarian carcinoma (EOC) remains unknown. In this study, HULC expression was examined in EOC, borderline and benign ovarian tumors, and normal ovarian tissues by RT-PCR. Ovarian cancer cell phenotypes, as well as autophagy-associated proteins were examined after HULC overexpression or downregulation by plasmid or small interfering RNA (siRNA) transfection, respectively. LncRNA-protein interactions were examined by ribonucleoprotein immunoprecipitation (RIP) assays. We found that HULC expression levels were higher in EOC tissues than normal samples. HULC overexpression induced cell proliferation, migration, invasion, whereas reduced cell apoptosis in vitro and induced tumor growth in vivo. In contrast, downregulation of HULC by siRNA transfection reduced cell proliferation, migration and invasion, and induced cell apoptosis and autophagy. Our results showed that HULC overexpression reduced ATG7, LC3-II and LAMP1 expression, while inducing SQSTM1 (P62) and ITGB1 expression. HULC downregulation had the opposite effects. Furthermore, RIP indicated that ATG7 interacted with HULC; ATG7 downregulation also induced cell proliferation, reduced apoptosis and inhibited autophagy in vitro by reducing LC3-II and LAMP1 expression, while inducing SQSTM1 expression. Furthermore, ATG7 co-transfection with HULC reversed the oncogenic effects of HULC both in vitro and in vivo; however, downregulating ATG7 did not affect cell migration and invasive ability. We found that ITGB1 siRNA co-transfection with HULC reversed the function of HULC in inducing ovarian cancer cell migration and invasive ability. Taken together, our results show that HULC may promote ovarian carcinoma tumorigenesis by inhibiting ATG7 and inducing progression by regulating ITGB1.


Epidemiological characteristics of lower extremity cellulitis after a typhoon flood.
The flood after a typhoon may lead to increase in patients with cellulitis of lower limbs. However, the microbiological features of these cases are rarely reported. We conducted a study of patients with lower extremity cellulitis after a typhoon followed in southern Taiwan to study the risk factors of cellulitis and the bacteriological features of the patients. We reviewed all the medical records of cellulitis at emergency departments of two teaching hospitals in southern Taiwan 30 days before and after the landing of Typhoon Morakot and collected data on the demographic and bacteriological characteristics. In addition, we evaluated the relationship between the daily number of patients and the rainfall in the Tainan area. The number of cellulitis patients increased from 183 to 344 during the 30-day period after the typhoon. The number peaked in the third and fourth days and lasted for 3 weeks. The proportion of patients with water immersion of the affected limb was higher after the typhoon (6% vs. 37%, odds ratio [OR]: 9.0, 95% Confidence interval [CI]: 4.7-17.2). We found cultures from the infected limbs with immersion had more polymicrobial (73% vs. 26%, OR: 7.8, 95% CI: 3.2-19.2) and Gram-negative bacilli infection (86% vs. 34%, OR: 11.8, 95% CI: 4.1-34.5). Flood arose from Typhoon Morakot caused increases in cellulitis patients, which lasted for 3 weeks. Antibiotic treatment that were effective to both Gram-positive cocci and Gram-negative bacilli are recommended for patients with limbs emerged in the water.


Catheter-directed gastric artery chemical embolization suppresses systemic ghrelin levels in porcine model.
To prospectively test, in a porcine model, the hypothesis that catheter-directed gastric artery chemical embolization (GACE) can result in suppression of systemic ghrelin levels and affect weight gain. This study, which had Animal Care and Use Committee approval, was performed in healthy, growing swine (weight range, 40-45 kg; n = 10). GACE was performed in five swine with the infusion of sodium morrhuate (125 mug) selectively into the gastric arteries that supply the fundus. Five control animals underwent a sham procedure with 5 mL of saline. Weight and fasting plasma ghrelin levels were obtained in animals at baseline and in weeks 1-4. Statistical testing for substantial differences in ghrelin blood levels over time and between treated and untreated animals was performed by using a cross-sectional time-series linear model with feasibility generalized least squares. The pattern of the change in ghrelin levels over time was significantly different between control and treated animals (P < .004). In treated animals, ghrelin levels were significantly reduced at week 1 (mean, 664.1 pg/mL +/- 103.1 [standard error of the mean], P < .02), week 2 (mean, 618.1 pg/mL +/- 180.4, P < .001), week 3 (mean, 578.4 pg/mL +/- 214.9, P < .001), and week 4 (mean, 876.6 pg/mL +/- 228.6, P < .03) relative to baseline (mean, 1006.3 pg/mL +/- 190.1). The percentage change in serum ghrelin values in swine treated with GACE decreased from baseline to -34%, -38.6%, -42.5%, and -12.9% during weeks 1-4, respectively. In control swine, percentage change in serum ghrelin was -1.7%, -9.7%, +2.6%, and +18.2% during weeks 1-4, respectively. At the end of 4 weeks, control swine continued to gain weight, with a 15.1% increase from their original weight, while the weight in swine treated with GACE plateaued at an increase of 7.8% from the original weight. Catheter-directed GACE can suppress the appetite hormone ghrelin and affect weight gain.


Prevalence of glucose-6-phosphate dehydrogenase deficiency and its association with Plasmodium falciparum infection among children in Iganga distric in Uganda.
Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic enzyme involved in the pentose phosphate pathway, its especially important in red blood cell metabolism. Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD. About 400 million people worldwide have a deficiency of this enzyme. The remarkable geographic correlation of G6PD deficiency distribution with historical endemicity patterns of malaria has led to suggestions that the two could be linked. Some studies have concluded that G6PD deficiency confers resistance to malaria. To determine the prevalence of G6PD deficiency, and determine its relationship with prevalence and incidence of P. falciparum infection among children in Uganda. This was longitudinal study involving 245 children, 135 were actively followed up for 12 months. G6PD status was assessed for using PCR-RFLP method. A thick smear was done to determine presence of plasmodium trophozoites and parasite densities. A total of 245 children between 6 months and 9 years were recruited. Of these 46.5% were males. Overall prevalence for the X-linked G6PD A- mutation was; 79.59% wild type, 12.65% heterozygous and 7.76% homozygous or hemizygous. Among the males 14% were hemizygous. At baseline, 40.8% had asymptomatic P falciparum infection. There was no statistically significant difference in prevalence and incidence rates of malaria infection among the different G6PD genotypes with prevalence among heterozygous, homozygous, and wild type being 29%, 42.6% and 43% respectively (p = 0.11) and incidence among heterozygous and wild type being 0.56 and 0.52 episodes/year (p = 0.5). The heterozygous G6PD A- females had a lower parasite density compared to the wild type (2505 vs 941 parasites/μL; P = 0.024). This study showed that 20.41% of the population in this part of Uganda carry the G6PD A-mutation, within the range of 15-32% seen in other parts of Africa. P. falciparum infection incidence and prevalence rates are similar among the G6PD genotypes though, once infected, P. falciparum parasite densities are lowest among G6PD A- heterozygous females. This suggests differences in P. falciparum infection rates and severity of disease could be mediated by differences in parasite densities among the different G6PD genotypes.


Adiponectin is associated with favorable lipoprotein profile, independent of BMI and insulin resistance, in adolescents.
Children with obesity and insulin resistance (IR) have decreased adiponectin and have increased cardiovascular risk. Adiponectin has antiatherogenic effects, but its mechanism is unclear. Our objectives were 1) to compare lipoprotein subclass particles among obese and lean adolescents and delineate their relationships with IR and 2) to measure relationships between adiponectin and lipoproteins and their dependence on body mass index (BMI) and/or IR. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURES: This was a cross-sectional study of 57 obese and 38 lean pubertal adolescents, measuring lipoprotein subclass particles (nuclear magnetic resonance spectroscopy), lipids, adiponectin, and homeostasis model assessment of IR (HOMA-IR). Obese had higher low-density lipoprotein (LDL) cholesterol (P = 0.018), higher small LDL particles (LDL-P) (P < 0.0005), smaller LDL-P size (P < 0.0005), smaller high-density lipoprotein particle (HDL-P) size (P < 0.0005), lower HDL cholesterol (HDL-C) (P < 0.0005), and higher small HDL-P (P = 0.009) compared with lean. HOMA-IR was higher in obese than lean (P < 0.0005) and positively associated with triglycerides, large very LDL-P, and small HDL-P and negatively with HDL-P size in obese. Adiponectin was lower in obese than lean (P < 0.0005) and was positively associated with LDL-P size, HDL-P size, and HDL-C and negatively with triglycerides, small LDL-P, large very LDL-P, and small HDL-P in obese. Using linear regression adjusting for demographics, Tanner stage, BMI, and HOMA-IR in all adolescents, adiponectin was positively associated with LDL-P size (P = 0.028), HDL-P size (P < 0.0005), and HDL-C (P = 0.042) and negatively with small LDL-P (P = 0.009) and small HDL-P (P = 0.004). Obese adolescents have lower adiponectin levels than lean, and a more atherogenic lipoprotein profile, associated with increased IR. Adiponectin was inversely associated with atherogenic lipoproteins in adolescents, even after adjusting for obesity and IR. This is the first such report in children, and suggests a relationship between adiponectin and lipoproteins in adolescents independent of BMI and IR.


Safety of Janssen Ad26.COV.S and Astra Zeneca AZD1222 COVID-19 Vaccines among Mobile Phone Users in Malawi: Findings from a National Mobile-Based Syndromic Surveillance Survey, July 2021 to December 2021.
The safety profiles of the Ad26.COV2.S and AZD1222 COVID-19 vaccines have not been described in the general population in Malawi. We present self-reported adverse events (AE) following the receipt of these vaccines in Malawi as part of a national syndromic surveillance survey. We conducted phone-based syndromic surveillance surveys among adults (≥18 years) with verbal consent. We used secure tablets through random digit dialing to select mobile phone numbers and collected data electronically. Survey questions included whether the respondent had received the COVID-19 vaccines, whether they had experienced any AE following vaccination, and the severity of the AE. We used multivariable analysis to identify factors associated with self-reported AE post-COVID-19 vaccination. A total of 11,924 (36.0%) out of 33,150 respondents reported receiving at least one dose of either Ad26.COV2.S or AZD1222 between July-December 2021; of those, 65.1% were female. About 49.2% of the vaccine recipients reported at least one AE, 90.6% of which were mild, and 2.6% were severe. Higher education level and concern about the safety of COVID-19 vaccines were associated with AE self-report (Adjusted Odds Ratio [AOR] 2.63 [95% CI 1.96-3.53] and 1.44, [95% CI 1.30-1.61], respectively), while male gender and older age were associated with reduced likelihood of AE self-report (AORs 0.81, [95% CI 0.75-0.88], 0.62 [95% CI 0.50-0.77], respectively). Ad26.COV2.S and AZD1222 vaccines are well-tolerated, with primarily mild and few severe AE among adults living in Malawi. Self-reporting of AE following COVID-19 vaccination is associated with gender, age, education, and concern about the safety of the vaccines. Recognizing these associations is key when designing and implementing COVID-19 vaccination communication messages to increase vaccination coverage.


Effects of psychological eating behaviour domains on the association between socio-economic status and BMI.
The current study investigates potential pathways from socio-economic status (SES) to BMI in the adult population, considering psychological domains of eating behaviour (restrained eating, uncontrolled eating, emotional eating) as potential mediators stratified for sex. Data were derived from the population-based cross-sectional LIFE-Adult-Study. Parallel-mediation models were conducted to obtain the total, direct and indirect effects of psychological eating behaviour domains on the association between SES and BMI for men and for women. Leipzig, Germany. We studied 5935 participants aged 18 to 79 years. Uncontrolled eating mediated the association between SES and BMI in men only and restrained eating in both men and women. Emotional eating did not act as mediator in this relationship. The total effect of eating behaviour domains on the association between SES and BMI was estimated as β=-0·03 (se 0·02; 95 % CI -0·062, -0·003) in men and β=-0·18 (se 0·02; 95 % CI -0·217, -0·138) in women. Our findings do not indicate a strong overall mediation effect of the eating behaviour domains restrained eating, uncontrolled eating and emotional eating on the association between SES and BMI. Further research on other pathways of this association is strongly recommended. Importantly, our findings indicate that, independent from one's social position, focusing on psychological aspects in weight reduction might be a promising approach.


Death-discordant twins--a new method to evaluate genetic factors in chronic diseases.
One of the most important lines of research on unselected large scale twin registries are mortality followups. Death-specific concordance rates have been calculated using different measures of concordance. These estimates are of great importance but they only reflect an "all or-none" classification of the genetic effect. It is suggested that mortality studies could be extended to, and include studies on, death-discordant twins. Such studies combine the advantages from mortality follow-ups on total twin populations with the detailed clinical investigation on subsamples. By examining the surviving cotwins with respect to various traits and supposed risk factors, an opportunity has been provided to study the genetic determination on the development of disease. This approach has been used in a study of ischaemic heart disease (IHD) and its risk factors in a representative subsample from the Swedish Twin Registry.


Relation of the Bilateral Earlobe Crease to Endothelial Dysfunction.
The presence of an earlobe crease (ELC) may be a simple sign to predict atherosclerosis. We evaluated the relation between ELC and vascular function. We measured flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) and observed bilateral earlobes in 400 consecutive subjects. At first, the subjects were divided into 3 groups: non-ELC group, unilateral ELC group, and bilateral ELC group. FMD and NID were significantly lower in the unilateral and bilateral ELC groups than those in the non-ELC group. After adjustment of cardiovascular risk factors, bilateral ELC, but not unilateral ELC, was associated with lower FMD and lower NID. We also investigated whether an increase in the number of ELCs worsens endothelial function, whether the difference in ELC structure (cross stripes and/or ramification) affects endothelial function, and whether endothelial function is impaired in subjects with superficial wrinkles depending on age. The number of ELCs, shape of the ELC, and superficial wrinkles were not associated with endothelial dysfunction. In conclusion, these findings suggest that the presence of bilateral ELCs is associated with vascular dysfunction.


Observation of Wigner crystal phase and ripplon-limited mobility behavior in monolayer CVD MoS2 with grain boundary.
Two-dimensional electron gas (2DEG) is crucial in condensed matter physics and is present on the surface of liquid helium and at the interface of semiconductors. Monolayer MoS2 of 2D materials also contains 2DEG in an atomic layer as a field effect transistor (FET) ultrathin channel. In this study, we synthesized double triangular MoS2 through a chemical vapor deposition method to obtain grain boundaries for forming a ripple structure in the FET channel. When the temperature was higher than approximately 175 K, the temperature dependence of the electron mobility μ was consistent with those in previous experiments and theoretical predictions. When the temperature was lower than approximately 175 K, the mobility behavior decreased with the temperature; this finding was also consistent with that of the previous experiments. We are the first research group to explain the decreasing mobility behavior by using the Wigner crystal phase and to discover the temperature independence of ripplon-limited mobility behavior at lower temperatures. Although these mobility behaviors have been studied on the surface of liquid helium through theories and experiments, they have not been previously analyzed in 2D materials and semiconductors. We are the first research group to report the similar temperature-dependent mobility behavior of the surface of liquid helium and the monolayer MoS2.


Surgical treatment of spontaneous endometriosis in rhesus macaques (Macaca mulatta): 11 cases (2007-2011).
OBJECTIVE To determine long-term outcome for rhesus macaques (Macaca mulatta) with endometriosis that underwent surgical treatment and identify factors potentially associated with long-term outcome. DESIGN Retrospective case series. ANIMALS 11 female rhesus macaques. PROCEDURES Medical records of female rhesus macaques in which endometriosis was diagnosed between 2007 and 2011 and that underwent abdominal exploratory surgery were reviewed. RESULTS In 5 macaques, the only clinical abnormality was a caudal abdominal mass identified during a routine physical examination, and in 6 macaques, overt clinical signs of endometriosis, including anorexia, dysmenorrhea, and lethargy during menses, were reported. Five macaques had histologically confirmed complete ovarian removal, and another 5 had incomplete ovarian removal (ovarian tissue was not examined histologically in 1 macaque). Nine animals survived at least 12 months after surgery, and 6 survived at least 60 months after surgery. Macaques that did not have overt clinical signs were significantly more likely to survive at least 60 months after surgery. However, extent of ovarian removal was not significantly associated with survival 12 or 60 months after surgery. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in select situations, surgery (ovariectomy or ovariohysterectomy) may be curative in macaques with endometriosis and may result in long-term survival. Further, findings suggested that monitoring until clinical signs appear before performing surgery is not warranted in adult female macaques suspected to have endometriosis that only have a caudal abdominal mass and no other overt clinical signs.


Protective effects of rosmarinic acid on doxorubicin-induced testicular damage.
We investigated the protective effects of rosmarinic acid (RA) on testicular damage induced by doxorubicin (DXR) in rats. In total, 21 rats were divided into 3 groups: the control group that received no treatment, the DXR group that received intraperitoneal (i.p.) DXR on day 7 and the DXR + RA group that received intragastric RA for 10 days with i.p. DXR on day 7. The rats were sacrificed on day 11 for histological and biochemical analyses. To assess oxidative damage, glutathione peroxidase (GPx) and malondialdehyde (MDA) levels were measured. The median modified Johnsen score of the DXR + RA group was higher than that of the DXR group (p = 0.002). The rats with the narrowest seminiferous tubules were in the DXR group (0.17 ± 0.03), and the difference between the DXR + RA and DXR groups was statistically significant (p = 0.002). The number of apoptotic cells in the DXR group was significantly higher than that in the control group, and there were significantly fewer apoptotic cells in the DXR + RA group than in the DXR group (p = 0.002). The MDA level was lowest in the control group and highest in the DXR group, and the level observed in the DXR + RA group significantly lower than that in the DXR group (p = 0.002). The GPx level was highest in the control group, with the level observed in the DXR + RA group significantly higher than that in the DXR group (p = 0.002). The testosterone level was lowest in the DXR group and highest in the control group, and that observed in the DXR + RA group was significantly higher than that in the DXR group (p = 0.018). RA can correct DXR-induced testicular damage through its antioxidant properties. However, the mechanism underlying the effects of RA requires further investigation, and long-term and comparative human studies are also needed.


An approximate model of polygenic inheritance.
The finite polygenic model approximates polygenic inheritance by postulating that a quantitative trait is determined by n independent, additive loci. The 3n possible genotypes for each person in this model limit its applicability. CANNINGS, THOMPSON, and SKOLNICK suggested a simplified, nongenetic version of the model involving only 2n + 1 genotypes per person. This article shows that this hypergeometric polygenic model also approximates polygenic inheritance well. In particular, for noninbred pedigrees, trait means, variances, covariances, and marginal distributions match those of the ordinary finite polygenic model. Furthermore as n --> infinity, the trait values within a pedigree collectively tend toward multivariate normality. The implications of these results for likelihood evaluation under the polygenic threshold and mixed models of inheritance are discussed. Finally, a simple numerical example illustrates the application of the hypergeometric polygenic model to risk prediction under the polygenic threshold model.


Role of infection in the pathogenesis of Alzheimer's disease: implications for treatment.
While our understanding of the neuropathology of Alzheimer's disease continues to grow, its pathogenesis remains a subject of intense debate. Genetic mutations contribute to a minority of early-onset autosomal dominant cases, but most cases are of either late-onset familial or sporadic form. CNS infections, most notably herpes simplex virus type 1, Chlamydophila pneumoniae and several types of spirochetes, have been previously suggested as possible aetiological agents in the development of sporadic Alzheimer's disease but with little consistent evidence. However, peripheral infections may have a role to play in accelerating neurodegeneration in Alzheimer's disease by activating already primed microglial cells within the CNS. Potential pharmacological interventions could aim at modification of this peripheral inflammatory response through targeting various agents involved in this inflammatory pathway. However, benefit could also be gained clinically through the meticulous detection, treatment and prevention of infections in individuals either alone or in combination with anti-inflammatory therapy.


Plant transducers of the endoplasmic reticulum unfolded protein response.
The unfolded protein response (UPR) activates a set of genes to overcome accumulation of unfolded proteins in the endoplasmic reticulum (ER), a condition termed ER stress, and constitutes an essential part of ER protein quality control that ensures efficient maturation of secretory and membrane proteins in eukaryotes. Recent studies on Arabidopsis and rice identified the signaling pathway in which the ER membrane-localized ribonuclease IRE1 (inositol-requiring enzyme 1) catalyzes unconventional cytoplasmic splicing of mRNA, thereby producing the active transcription factor Arabidopsis bZIP60 (basic leucine zipper 60) and its ortholog in rice. Here we review recent findings identifying the molecular components of the plant UPR, including IRE1/bZIP60 and the membrane-bound transcription factors bZIP17 and bZIP28, and implicating its importance in several physiological phenomena such as pathogen response.


Anxiety and Problematic Internet Use in Tunisian students.
The timing of this study coincides with the growing rate of penetration of Internet service across the country. However, it is predictable that any new technology may be associated with a variety of human responses, sometimes harmfull. The young students seem to be especially vulnerable. The purposes of this study were to evaluate Problematic Internet Use among medical undergraduate students and to investigate for associated anxious symptoms. We conducted a cross-sectional study on 120 students enrolled in undergraduate medical studies at the University of Medicine of Sfax- Tunisia. The self-administered Young's 8-item questionnaire was used in this survey. The state and trait anxiety inventory was administered to screen for anxiety symptoms. The results showed that 21.7% of the students have Problematic Internet Use (PIU).The rate of the PIU is greater in male students than infemale students (p=0.035). Anxiety trait was significantly associated in students with PIU compared to those without PIU (p=0.002). Anxiety state was significantly associated in students with PIU compared to those without PIU ( p = 0.003). Problematic Internet Use is frequent in our students population. Asking students about the characteristics of their Internet usage will help to determine the threats to which they might be exposed. Such association with other psychopathologic problems, especially anxiety, should be sought.


Efficacy and safety of CKD-495 in acute and chronic gastritis: A Phase III superiority clinical trial.
Despite the availability of numerous treatment options, many patients with gastritis experience only partial symptom relief. CKD-495, a newly developed product with the active ingredient extracted from Cinnamomum cassia Presl., has demonstrated anti-inflammatory and antioxidant activity in vitro and an in vivo protective effect against gastric damage by stimulating mucus secretion. This study compared the efficacy and safety of CKD-495 with Artemisiae argyi folium (AAF) for the treatment of acute and chronic gastritis. AAF, a gastric mucosa protective agent that promotes gastric mucosa regeneration, has been used clinically for about 20 years. This phase III multicenter, randomized, double-blind, parallel-group trial (ClinicalTrials.gov; NCT04255589) assigned 242 patients with endoscopically-proven gastric mucosal erosions to receive CKD-495 75 mg (n = 122) or AAF 60 mg (n = 120), respectively, with placebo (for double-blind purposes) 3 times a day for 2 weeks. The primary efficacy endpoint was the erosion improvement rate. Secondary endpoints included erosion cure rates, and improvement rates for edema, redness, hemorrhage, and gastrointestinal (GI) symptoms. Drug-related adverse events were evaluated. The erosion improvement rate was significantly higher in the CKD-495 group than in the AAF group for both the full analysis set (55.9% vs 39.4%, P = .0063) and per-protocol set (54.6% vs 38.2%, P = .0084). In addition, the erosion improvement rate in patients with acute or chronic gastritis showed that the CKD-495 group had better improvement of erosion than the AAF group, especially in patients with chronic gastritis. Analysis of secondary endpoints, which included erosion cure rate and the improvement rates of edema, redness, hemorrhage, and GI symptoms, showed that the CKD-495 group was more effective than the AAF group. There were no significant between-group differences in safety profiles. No serious adverse events or adverse drug reactions occurred. These results demonstrate that CKD-495 75 mg is superior to AAF 60 mg in terms of the endoscopic improvement rate of erosions in patients with acute or chronic gastritis. This new mucoprotective agent, CKD-495, can be considered the therapy of choice for symptomatic relief and healing of gastritis.


Saturday conference: non-hodgkin's lymphoma.
The non-Hodgkin's lymphomas represent an area of rapid medical progress. Recent studies of staging have suggested that with respect to therapy disease is either limited (stage I or II) or advanced (stage III or IV). Bone marrow biopsy is important as an initial staging tool, and retroperitoneal evaluation (lymphangiography, ultrasound) is important when marrow involvement is not present and also as a means of establishing a baseline for clinical evaluation. For patients with nodular lymphoma, combination chemotherapy can produce high rates of complete remission, but relapses occur and survival has not been shown to be improved as compared to patients receiving single-agent therapy; the value of therapy is asymptomatic patients is not established. In contrast, advanced histiocytic lymphoma, which is rapidly fatal when single-agent therapy is used, is cured in half of patients receiving new combination chemotherapy regimens. While clinical discussions must use the Rappaport system of pathologic classification, because most data have been expressed using this terminology, it should be recognized that immunologic approaches to the classification of lymphoma exist, and that their clinical utility is undergoing evaluation.


Step-by-step guide to post-acquisition correlation of confocal and FIB/SEM volumes using Amira software.
In recent years new methodologies and workflow pipelines for acquiring correlated fluorescence microscopy and volume electron microscopy datasets have been extensively described and made accessible to users of different levels. Post-acquisition image processing, and particularly correlation of the optical and electron data in a single integrated three-dimensional framework can be key for extracting valuable information, especially when imaging large sample volumes such as whole cells or tissues. These tasks remain challenging and are often rate-limiting to most users. Here we provide a step-by-step guide to image processing and manual correlation using ImageJ and Amira software of a confocal microscopy stack and a focused ion beam/scanning electron microscopy (FIB/SEM) tomogram acquired using a correlative pipeline. These previously published datasets capture a highly transient invasion event by the bacterium Shigella flexneri infecting an epithelial cell grown in culture, and are made available here in their pre-processed form for readers who wish to gain hands-on experience in image processing and correlation using existing data. In this guide we describe a simple protocol for correlation based on internal sample features clearly visible by both fluorescence and electron microscopy, which is normally sufficient when correlating standard fluorescence microscopy stacks with FIB/SEM data. While the guide describes the treatment of specific datasets, it is applicable to a wide variety of samples and different microscopy approaches that require basic correlation and visualization of two or more datasets in a single integrated framework.


Mucus colonization as a determinant of pathogenicity in intestinal infection by Campylobacter jejuni: a mouse cecal model.
Human isolates of the intestinal pathogen Campylobacter jejuni have been shown to colonize mucus on the outer surface and deep within the intestinal crypts of gnotobiotic or germfree mice. The cecal crypts are preferentially colonized. A model of mucus colonization by C. jejuni in the mouse cecum has been developed, using antibiotic- and magnesium sulfate-treated specific-pathogen-free animals. These spiral-shaped bacteria colonize the mucus in a similar manner to the normal spiral-shaped microbiota. No evidence of adhesion to the intestinal surface was found with a wide variety of microscopic techniques. The campylobacters were seen to be highly motile in living preparations of gut tissue and rapidly tracked along intestinal mucus. Just as many of the normal spiral-shaped bacteria of intestinal surfaces can achieve close association with the epithelium through mucus association and do not adhere to the surface, C. jejuni colonizes the intestinal mucosa via mucus colonization. Thus, a major determinant of pathogenicity in intestinal infection with C. jejuni is proposed to be an ability to colonize intestinal mucus. The possession of specific adhesins is unlikely to be a significant determinant of pathogenicity. Better understanding of the mechanism of mucus association and the properties of the bacterium that are responsible will provide a basis for the rational selection of preventative measures. The model of mucus association in adult antibiotic-treated mice provides an opportunity for colonization studies with variant organisms and immunization studies.


Secondary Philadelphia chromosome and erythrophagocytosis in a relapsed acute myeloid leukemia after hematopoietic cell transplantation.
The acquisition of the Philadelphia chromosome (Ph) as a secondary change during the course of hematopoietic malignancies is rare and is associated with poor prognosis. Few cases of secondary Ph have been reported after hematopoietic cell transplantation (HCT). A secondary Ph at relapse is of clinical importance because it provides a therapeutic target for tyrosine kinase inhibitors along with or in replacement of chemotherapy. We describe a case of relapsed acute myeloid leukemia (AML) after HCT that developed a BCR-ABL1 translocation along with erythrophagocytosis by blasts as a secondary change at the time of relapse. The progression of this patient's myeloid neoplasm from myelodysplastic syndrome to AML to relapsed AML after HCT was accompanied by a stepwise cytogenetic evolution: A deletion 20q abnormality subsequently acquired a deletion 7q and, finally, at relapse after HCT, a secondary Ph was gained. The relationship between the secondary Ph and the erythrophagocytosis by blasts is not clear. We review the possible pathogenesis and cytogenetic associations of erythrophagocytosis by blasts, a rare feature in acute leukemias.


Mechanistic insights into an engineered riboswitch: a switching element which confers riboswitch activity.
While many different RNA aptamers have been identified that bind to a plethora of small molecules only very few are capable of acting as engineered riboswitches. Even for aptamers binding the same ligand large differences in their regulatory potential were observed. We address here the molecular basis for these differences by using a set of unrelated neomycin-binding aptamers. UV melting analyses showed that regulating aptamers are thermally stabilized to a significantly higher degree upon ligand binding than inactive ones. Regulating aptamers show high ligand-binding affinity in the low nanomolar range which is necessary but not sufficient for regulation. NMR data showed that a destabilized, open ground state accompanied by extensive structural changes upon ligand binding is important for regulation. In contrast, inactive aptamers are already pre-formed in the absence of the ligand. By a combination of genetic, biochemical and structural analyses, we identified a switching element responsible for destabilizing the ligand free state without compromising the bound form. Our results explain for the first time the molecular mechanism of an engineered riboswitch.


OASTL-A1 functions as a cytosolic cysteine synthase and affects arsenic tolerance in rice.
Arsenic (As) contamination in paddy soil can cause phytotoxicity and elevated As accumulation in rice grains. Arsenic detoxification is closely linked to sulfur assimilation, but the genes involved have not been described in rice. In this study, we characterize the function of OASTL-A1, an O-acetylserine(thiol) lyase, in cysteine biosynthesis and detoxification of As in rice. Tissue expression analysis revealed that OsOASTL-A1 is mainly expressed in roots at the vegetative growth stage and in nodes at the reproductive stage. Furthermore, the expression of OsOASTL-A1 in roots was strongly induced by As exposure. Transgenic rice plants expressing pOsOASTL-A1::GUS (β-glucuronidase) indicated that OsOASTL-A1 was strongly expressed in the outer cortex and the vascular cylinder in the root mature zone. Subcellular localization using OsOASTL-A1:eGFP (enhanced green fluorescent protein) fusion protein showed that OsOASTL-A1 was localized to the cytosol. In vivo and in vitro enzyme activity assays showed that OsOASTL-A1 possessed the O-acetylserine(thiol) lyase activity. Knockout of OsOASTL-A1 led to significantly lower levels of cysteine, glutathione, and phytochelatins in roots and increased sensitivity to arsenate stress. Furthermore, the osoastl-a1 knockout mutants reduced As accumulation in the roots, but increased As accumulation in shoots. We conclude that OsOASTL-A1 is the cytosolic O-acetylserine(thiol) lyase that plays an important role in non-protein thiol biosynthesis in roots for As detoxification.


Infections with extended-spectrum beta-lactamase-producing enterobacteriaceae: changing epidemiology and drug treatment choices.
Since 2000, Escherichia coli producing CTX-M enzymes (especially CTX-M-15) have emerged worldwide as important causes of community-onset urinary tract infections (UTIs) and bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing bacteria. Molecular epidemiology studies suggested that the sudden worldwide increase of CTX-M-15-producing E. coli is mostly due to a single clone named ST131 and that foreign travel to high-risk areas such as the Indian subcontinent might in part play a role in the spread of this clone across different continents. Empirical antibacterial coverage for these resistant organisms should be considered in community patients presenting with sepsis involving the urinary tract especially if a patient recently travelled to a high-risk area. Infections due to ESBL-producing Enterobacteriaceae are associated with a delay in initiation of appropriate antibacterial therapy, which consequently prolongs hospital stays and increases hospital costs. Failure to initiate appropriate antibacterial therapy from the start appears to be responsible for higher patient mortality. The carbapenems are widely regarded as the drugs of choice for the treatment of severe infections due to ESBL-producing Enterobacteriaceae, although comparative clinical trials are lacking. Agents that may be useful for the treatment of ESBL-associated UTIs include fosfomycin, nitrofurantoin and temocillin. If this emerging public health threat is ignored, it is possible that clinicians may be forced in the near future to use the carbapenems as the first choice for empirical treatment of serious infections associated with UTIs originating from the community.


Hypertrophic cardiomyopathy--state of the art in 2007.
Hypertrophic cardiomyopathy (HCM) is a primary disease of the sarcomere, with considerable genetic heterogeneity and variability in phenotypic expression, whose main complication is sudden cardiac death (SCD). Genetic aspects of HCM, its molecular pathophysiology and genotype-phenotype relationships are the subject of this review, which is aimed at better understanding of practical management in this patient population. As HCM is a genetic disease whose initial manifestation can be sudden death, it is essential to establish the diagnosis at an early stage, to proceed with risk stratification and implementation of SCD prevention strategies, and to promote genetic counseling of patients and screening of their families. Detection of pathological mutations through progressive sequencing of the genes most commonly involved is the most efficient way to diagnose HCM, even in the absence of clinical evidence of the disease. Identification of individuals at high risk of SCD is a major challenge in the management of this population, since SCD can be prevented by use of an implantable cardioverter-defibrillator. The selection of patients for prophylactic implantation of these devices, particularly those who have only one major risk factor, is currently the subject of controversy.


Global gene expression responses to low- or high-dose radiation in a human three-dimensional tissue model.
Accumulating data suggest that the biological responses to high and low doses of radiation are qualitatively different, necessitating the direct study of low-dose responses to better understand potential risks. Most such studies have used two-dimensional culture systems, which may not fully represent responses in three-dimensional tissues. To gain insight into low-dose responses in tissue, we have profiled global gene expression in EPI-200, a three-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 h after exposure to high (2.5 Gy) and low (0.1 Gy) doses of low-LET protons. The most significant gene ontology groups among genes altered in expression were consistent with effects observed at the tissue level, where the low dose was associated with recovery and tissue repair, while the high dose resulted in loss of structural integrity and terminal differentiation. Network analysis of the significantly responding genes suggested that TP53 dominated the response to 2.5 Gy, while HNF4A, a novel transcription factor not previously associated with radiation response, was most prominent in the low-dose response. HNF4A protein levels and phosphorylation were found to increase in tissues and cells after low- but not high-dose irradiation.


Genetic dissection of rice grain shape using a recombinant inbred line population derived from two contrasting parents and fine mapping a pleiotropic quantitative trait locus qGL7.
The three-dimensional shape of grain, measured as grain length, width, and thickness (GL, GW, and GT), is one of the most important components of grain appearance in rice. Determining the genetic basis of variations in grain shape could facilitate efficient improvements in grain appearance. In this study, an F7:8 recombinant inbred line population (RIL) derived from a cross between indica and japonica cultivars (Nanyangzhan and Chuan7) contrasting in grain size was used for quantitative trait locus (QTL) mapping. A genetic linkage map was constructed with 164 simple sequence repeat (SSR) markers. The major aim of this study was to detect a QTL for grain shape and to fine map a minor QTL, qGL7. Four QTLs for GL were detected on chromosomes 3 and 7, and 10 QTLs for GW and 9 QTLs for GT were identified on chromosomes 2, 3, 5, 7, 9 and 10, respectively. A total of 28 QTLs were identified, of which several are reported for the first time; four major QTLs and six minor QTLs for grain shape were also commonly detected in both years. The minor QTL, qGL7, exhibited pleiotropic effects on GL, GW, GT, 1000-grain weight (TGW), and spikelets per panicle (SPP) and was further validated in a near isogenic F2 population (NIL-F2). Finally, qGL7 was narrowed down to an interval between InDel marker RID711 and SSR marker RM6389, covering a 258-kb region in the Nipponbare genome, and cosegregated with InDel markers RID710 and RID76. Materials with very different phenotypes were used to develop mapping populations to detect QTLs because of their complex genetic background. Progeny tests proved that the minor QTL, qGL7, could display a single mendelian characteristic. Therefore, we suggested that minor QTLs for traits with high heritability could be isolated using a map-based cloning strategy in a large NIL-F2 population. In addition, combinations of different QTLs produced diverse grain shapes, which provide the ability to breed more varieties of rice to satisfy consumer preferences.


Reassessment of the Listeria monocytogenes pan-genome reveals dynamic integration hotspots and mobile genetic elements as major components of the accessory genome.
Listeria monocytogenes is an important food-borne pathogen and model organism for host-pathogen interaction, thus representing an invaluable target considering research on the forces governing the evolution of such microbes. The diversity of this species has not been exhaustively explored yet, as previous efforts have focused on analyses of serotypes primarily implicated in human listeriosis. We conducted complete genome sequencing of 11 strains employing 454 GS FLX technology, thereby achieving full coverage of all serotypes including the first complete strains of serotypes 1/2b, 3c, 3b, 4c, 4d, and 4e. These were comparatively analyzed in conjunction with publicly available data and assessed for pathogenicity in the Galleria mellonella insect model. The species pan-genome of L. monocytogenes is highly stable but open, suggesting an ability to adapt to new niches by generating or including new genetic information. The majority of gene-scale differences represented by the accessory genome resulted from nine hyper variable hotspots, a similar number of different prophages, three transposons (Tn916, Tn554, IS3-like), and two mobilizable islands. Only a subset of strains showed CRISPR/Cas bacteriophage resistance systems of different subtypes, suggesting a supplementary function in maintenance of chromosomal stability. Multiple phylogenetic branches of the genus Listeria imply long common histories of strains of each lineage as revealed by a SNP-based core genome tree highlighting the impact of small mutations for the evolution of species L. monocytogenes. Frequent loss or truncation of genes described to be vital for virulence or pathogenicity was confirmed as a recurring pattern, especially for strains belonging to lineages III and II. New candidate genes implicated in virulence function were predicted based on functional domains and phylogenetic distribution. A comparative analysis of small regulatory RNA candidates supports observations of a differential distribution of trans-encoded RNA, hinting at a diverse range of adaptations and regulatory impact. This study determined commonly occurring hyper variable hotspots and mobile elements as primary effectors of quantitative gene-scale evolution of species L. monocytogenes, while gene decay and SNPs seem to represent major factors influencing long-term evolution. The discovery of common and disparately distributed genes considering lineages, serogroups, serotypes and strains of species L. monocytogenes will assist in diagnostic, phylogenetic and functional research, supported by the comparative genomic GECO-LisDB analysis server (http://bioinfo.mikrobio.med.uni-giessen.de/geco2lisdb).


Embryonic and uterine factors in delayed implantation in rodents.
An hypothesis for delayed implantation and embryonic quiescence is proposed on the basis of adaptation of blastocysts to changes in their environment. The environmental factors considered consist of macromolecules and essential ions and metabolites such as Ca2+, Mg2+ and glucose. Macromolecules appear to induce an influx of these essential metabolites which is followed by metabolic enhancement in blastocysts in the absence of any of the essential factors, the initial stages of embryonic diapause follow. The prevention of influx of metabolites such as Ca2+ by specific inhibitors, D600 or papaverine, also prevents activation of blastocysts. Early cleavage stage embryos show little or no response to changes in environmental macromolecules which may explain why embryos usually enter into quiescence at the blastocyst stage when the environmental constraints on blastocyst development become very marked. This also coincides with termination of cleavage and initiation of cell growth in embryos. The increase in responsiveness of embryos is attributed to several inherent changes including cell surface and functional changes in the plasma membrane. The conditions for embryonic quiescence in vivo are not species specific. Trophoblastic vesicles without the inner cell mass can also enter into quiescence. Studies using the antibiotic, tunicamycin, which inhibits protein glycosylation and prevents trophoblast adhesion and giant cell outgrowths, suggest that the cell surface interactions may involve glycoproteins. Such interactions may be crucial for implantation as well as for maintaining embryos in diapause for prolonged periods of time. A short sojourn in diapause for certain blastocysts which do not normally develop to an advanced stage, appears to have a beneficial effect on subsequent development. The overall significance of this suggestion for other species showing obligatory diapause is unclear.